Search

Abstract Background The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. Methods 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. Results In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. Conclusions A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.

Rare earth elements (REEs) have gained attention as tracers of pedogenic processes over the last few decades. Clay-sized fractions (CSFs, < 2 μm) may play a crucial role in hosting REEs. To better understand the pedochemical signals of REEs in clay-sized phases, such as iron oxides and phyllosilicates, we analyzed REE speciation in CSFs of carbonate rocks (limestone), clastic rocks (sandstone and shale), and their derived saprolites. Our results quantified the REE content (41.2–144.6 mg kg−1) and speciation in CSFs of parent materials, revealing that REEs were primarily hosted in amorphous iron oxides (Feox1), followed by crystalline iron oxides (Feox2) and phyllosilicates. Compared to parent materials, saprolites derived from carbonate rocks exhibited more than a two-fold enrichment of REEs in major clay-sized phases, confirming the role of CSFs as REE sinks during carbonate rock weathering. Furthermore, the initial REE patterns of CSFs of carbonate rocks underwent alteration throughout the weathering process, likely due to water–mineral interactions. Our findings suggest that REEs in CSFs record the weathering fingerprint for soils derived from carbonate rocks, while they are indicative of provenance for soils originating from clastic rocks.

Abstract Introduction Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. Objective The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. Methods MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. Results A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. Conclusion LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.

Abstract Background Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear. Methods Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling. Results CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1–CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK–STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production. Conclusions The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.

To explore the inhibitory effect of total glycosides of Cistanche deserticola (TG) on HepG2 cells and its mechanism. In this paper, different concentrations (0, 3.5, 10.5, 21, 31.5, 42 μg/mL) TG were treated 24 h on HepG2 liver cancer cells, and the viability of HepG2 cells was detected using CCK8 assay. Hoechst 33342/PI double staining method and Annexin V-FITC/PI were used to detect HepG2 cells apoptosis. The phenomenon of cell migration was detected by cell migration assay. Meanwhile, cell cycle progression changes were detected by flow cytometry. And the expression of α-fetoprotein (AFP), β-catenin, Dishevelled (Dsh), GSK-3β were detected by Western blot. The results showed that TG could reduce the proliferation of HepG2 cells in a concentration dependent manner, with only 31.04% cell viability when TG was 42 μg/mL. In addition, TG could damage the cell structure and induce cell apoptosis, and the apoptosis rate could be as high as 32.44% by AV/PI detection. Moreover, TG could also promote cell necrosis, and limit cell migration. There were significant differences between the treated group and the control group (P

Abstract Background Brainstem stroke causes severe and persistent neurological impairment. Due to the limited spontaneous recovery and regeneration of the disrupted neural circuits, transplantation of exogenous neural stem cells (NSCs) was an alternative, while there were limitations for primitive NSCs. Methods We established a mouse model of brainstem stroke by injecting endothelin in the right pons. Brain-derived neurotrophic factor (BDNF)- and distal-less homeobox 2 (Dlx2)-modified NSCs were transplanted to treat brainstem stroke. Transsynaptic viral tracking, immunostaining, magnetic resonance imaging, behavioral testing, and whole-cell patch clamp recordings were applied to probe the pathophysiology and therapeutic prospects of BDNF- and Dlx2-modified NSCs. Results GABAergic neurons were predominantly lost after the brainstem stroke. No endogenous NSCs were generated in situ or migrated from the neurogenesis niches within the brainstem infarct region. Co-overexpressions of BDNF and Dlx2 not only promoted the survival of NSCs, but also boosted the differentiation of NSCs into GABAergic neurons. Results from transsynaptic virus tracking, immunostaining, and evidence from whole-cell patch clamping revealed the morphological and functional integration of the grafted BDNF- and Dlx2-modified NSCs-derived neurons with the host neural circuits. Neurological function was improved by transplantation of BDNF- and Dlx2-modified NSCs in brainstem stroke. Conclusions These findings demonstrated that BDNF- and Dlx2-modified NSCs differentiated into GABAergic neurons, integrated into and reconstituted the host neural networks, and alleviated the ischemic injury. It thus provided a potential therapeutic strategy for brainstem stroke.

Tunnel construction in karst areas greatly impacts the local hydrological conditions. The drawdown of groundwater levels and the loss of soil water storage due to tunneling limit the available water resources on the karst land surface, and this may affect the function of plants. Here, we evaluated the responses of the radial growth rates of two major tree species (Masson pine and Camphor laurel) to a tunneling induced water stress event in a typical karst trough valley. Meanwhile, to discuss the overall influence of tunnel excavation on plant growth in all vegetation cover types, the dynamics of vegetation productivity around the tunnel were evaluated using remote sensing indices, the Normalized Difference Vegetation Index (NDVI), and Net Primary Productivity (NPP). Furthermore, we estimated the spatial–temporal variations of NDVI and NPP in other tunneling regions of Southwest China. The results showed that the soil moisture contents (SMC) around the Zhongliang Mountain Railway Line 6 (ZMRL6) tunnel had dramatically declined −5.06%∼−10.53% within the areas

To study the nutritional value and antioxidant activities of Cistanche deserticola Y. C. Ma extract. The water extraction method was used in this experiment to research the effects of different extraction conditions on the dry extract rate of Cistanche deserticola Y. C. Ma. Then the response surface analysis method was further used to optimize the process. Moreover, the nutritional components and functional components of the extract were determined, and the antioxidant function and effects on the life span and fecundity of C. elegans were discussed. The results showed that when the material liquid ratio was 1:12 g/mL, the decocting time was 140 min, and the decocting times were 4 times, the dry extract yield of the aqueous extract of Cistanche (AEC) was 65.83%±0.87%. In addition, the nutritional composition and functional components of AEC was detected and found to contain a large amount of nutritional components such as protein (5.22±0.44 g/100 g), fat (0.150±0.06 g/100 g), amino acids (0.640±0.05 g/100 g), etc, and echinacoside (557±4.24 mg/100 g), acteoside (169±7.07 mg/100 g), total sugar (22.1±0.64 g/100 g), total flavonoids (4.13±0.08 g/100 g) and others. Furthermore, the AEC also showed good DPPH scavenging activity, hydroxyl radical scavenging activity, total antioxidant activity, and reducing activity, all of which were concentration dependent. Finally, AEC could prolong the life span of Caenorhabditis elegans. Among them, 8 mg/mL AEC had the best effect, and its average life span reached 10.95±2.40 d. Therefore, AEC has good antioxidant capacity, and rich in various nutrients and functional components, which indicates that Cistanche deserticola Y. C. Ma has the potential to develop functional food antioxidants and provides a theoretical basis for the clinical application of Cistanche deserticola Y. C. Ma in the future.

Abstract Rationally constructing atom‐precise active sites is highly important to promote their catalytic performance but still challenging. Herein, this work designs and constructs ZSM‐5 supported Cu and Ag dual single atoms as a proof‐of‐concept catalyst (Ag1−Cu1/ZSM‐5 hetero‐SAC (single‐atom catalyst)) to boost direct oxidation of methane (DOM) by H2O2. The Ag1−Cu1/ZSM‐5 hetero‐SAC synthesized via a modified co‐adsorption strategy yields a methanol productivity of 20,115 µmol gcat−1 with 81% selectivity at 70 °C within 30 min, which surpasses most of the state‐of‐the‐art noble metal catalysts. The characterization results prove that the synergistic interaction between silver and copper facilitates the formation of highly reactive surface hydroxyl species to activate the C−H bond as well as the activity, selectivity, and stability of DOM compared with SACs, which is the key to the enhanced catalytic performance. This work believes the atomic‐level design strategy on dual‐single‐atom active sites should pave the way to designing advanced catalysts for methane conversion.

The acoustic and physical properties of two valuable marine cold spring carbonate rock samples gathered from the Chaoshan Depression in the South China Sea were measured. The Wyllie time-average equation was applied to analyze the measured sound speeds and their trend under different porosities, and the sound speeds of marine cold spring carbonate rocks were found to be consistent with those of terrestrial carbonate rocks. The Voigt model, Reuss model, and Voigt-Reuss-Hill model were used to predict the characteristics of the sound speed for four states of seafloor sediments containing cold spring carbonate mineral particles or rocks. For these four states of marine cold spring carbonate mineral particles existing on or in seafloor sediments, the sound speed and reflection coefficient of a mixture of seafloor surface sediments containing cold spring carbonate mineral particles or rocks decrease with an increase in the volume ratio of the seafloor sediment. This method for predicting the reflection coefficient provides evidence to explain the high and low reflection coefficients observed in Chirp sub-bottom profiles of cold spring seepage areas.

Abstract Background Given the rapid development of clinical immunology technologies, students majoring in laboratory medicine should master the technological principles and application of clinical laboratory immunology. However, many are required to take online courses due to COVID-19 restrictions, which highlights the need to revisit teaching strategies. Recently, various medical education courses (such as Biochemistry, Physiology, etc.) have implemented the flipped classroom (FC) and team-based learning (TBL) methods, resulting in more positive teaching evaluations. To promote the students' mastery of the difficult knowledge effectively during the online teaching work, we evaluated the performance of online FC-TBL in a clinical laboratory immunology course. Methods Sixty-two third-year students from two classes majoring in Laboratory Medicine were recruited and divided into two groups, including one group with traditional lecture-based learning teaching strategy (LBL group) and the other group with LBL or online FC combined with TBL teaching strategy (FC-TBL group). We selected three chapters to conduct FC-TBL teaching in class. All participants took in-class quizzes and final examinations that targeted the same knowledge points. Finally, all participants completed anonymous questionnaires asking for their perceptions of the respective teaching models. In addition, we conducted a survey of teaching suggestions by a FC-TBL class of students majoring in Laboratory Medicine. Results The FC-TBL group (vs LBL group) had significantly higher scores on the in-class quizzes and final examinations, and also reported high satisfaction with the FC-TBL model. These findings indicate that FC-TBL is suitable for clinical laboratory immunology, as the participants quickly gained essential knowledge. Specifically, FC-TBL helped to “increase learning motivation,” “promote self-directed learning skills,” “extend more related knowledge,” “enhance problem-solving abilities,” “enhance clinical reasoning abilities,” and “enhance communication skills.” For participants’ suggestions, 48.38% (15/31) students held positive attitude to FC-TBL teaching strategy compared to 25.81% (8/31) students who considered FC-TBL teaching strategy still needs continuous improvement, and 25.81% (8/31) students reported that they believed FC-TBL teaching strategy was perfect and no further suggestions. Conclusions Online FC-TBL effectively enhanced learning activity among students of a clinical laboratory immunology course. This is particularly useful in the COVID-19 context.

Abstract Background Triglyceride-glucose (TyG) index is a simple and reliable surrogate marker of insulin resistance. Elevated TyG index was related to stroke recurrence. This study aimed to explore the associations between TyG index with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion. Methods From November 1, 2016 to February 28, 2021, consecutive acute ischemic stroke patients admitted within 1 week after onset were screened. The stroke mechanism was determined based on medical history, laboratory examinations, cardiac examinations, vascular examinations and neuroimaging. Nondiabetic patients with small vessel occlusion were enrolled and followed up for 1 year. The primary outcome was ischemic stroke recurrence. Logistic regression and Kaplan–Meier survival curve were used to analyze the association of the TyG index and stroke recurrence. Results A total of 6100 acute ischemic stroke patients were screened, with 1970 nondiabetic patients with small vessel occlusion included and divided into 4 groups according to the TyG index quartiles (Q1: 8.92). There were significant differences in age, body mass index, systolic blood pression, diastolic blood pressure, lipid-lowering agents, infarct location, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, uric acid, and stroke recurrence among the 4 groups. In the multi-adjusted models, compared to Q1 of the TyG index, the odds ratio for Q4 of the TyG index for stroke recurrence was 3.100 (1.366–8.019). The Kaplan–Meier survival (ischemic stroke-free) curves by quartiles of the TyG index also showed statistically significant differences (log-rank test, P = 0.004). Conclusions Our findings suggested that the TyG index was associated with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion, and it could be a valuable biomarker for assessing the risk of ischemic stroke recurrence in these patients.

Cistanche is a tonic Chinese medicine commonly used in traditional Chinese medicine, with 2016, CFSA through the alxa desert cistanche safety evaluation, cistanche began to officially enter the food field. At present, the research on cistanche mainly focuses on the extraction, isolation and purification and pharmacological effects, and its pharmacological effects such as neuroprotective effects, immunomodulation, antioxidant anticancer and hepatoprotective liver protection have attracted the attention of researchers. This review mainly reviews the research status, chemical composition and health benefits, analyzes its application prospects in food, and aims to provide certain theoretical support for the safe application of cistanche in functional food.

Background and PurposeHyperglycemia has been associated with unfavorable outcome of acute ischemic stroke, but this association has not been verified in patients with endovascular thrombectomy treatment. This study aimed to assess the impact of stress hyperglycemia ratio on early neurological deterioration and favorable outcome after thrombectomy in patients with acute ischemic stroke.MethodsStroke patients with endovascular thrombectomy in two comprehensive centers were enrolled. Early neurological deterioration was defined as ≥4 points increase of National Institutes of Health Stroke Scale (NIHSS) at 24 hours after endovascular procedure. Favorable outcome was defined as modified Rankin Scale (mRS) score of 0-2 at 90 days of stroke onset. Multivariate regression analysis was used to identify the predictors for early neurological deterioration and favorable outcome.ResultsAmong the 559 enrolled, 74 (13.2%) patients developed early neurological deterioration. The predictors for early neurological deterioration were high stress hyperglycemia ratio at baseline (OR =5.77; 95% CI, 1.878-17.742; P =0.002), symptomatic intracranial hemorrhage (OR =4.90; 95% CI, 2.439-9.835; P

Developing single atom systems with improved catalytic potential for bio-application has major therapeutic potential. Here, the authors report on the development of a metal single-atom on a carbon dot support confined within mesoporous silica for the development of therapeutic agents.

BackgroundSpatial transcriptomics (STs) simultaneously obtains the location and amount of gene expression within a tissue section. However, current methods like FindMarkers calculated the differentially expressed genes (DEGs) based on the classical statistics, which should abolish the spatial information.Materials and methodsA new method named spatial analysis of spatial transcriptomics (saSpatial) was developed for both the location and the amount of gene expression. Then saSpatial was applied to detect DEGs in both inter- and intra-cross sections. DEGs detected by saSpatial were compared with those detected by FindMarkers.ResultsSpatial analysis of spatial transcriptomics was founded on the basis of spatial statistics. It was able to detect DEGs in different regions in the normal brain section. As for the brain with ischemic stroke, saSpatial revealed the DEGs for the ischemic core and penumbra. In addition, saSpatial characterized the genetic heterogeneity in the normal and ischemic cortex. Compared to FindMarkers, a larger number of valuable DEGs were found by saSpatial.ConclusionSpatial analysis of spatial transcriptomics was able to effectively detect DEGs in STs data. It was a simple and valuable tool that could help potential researchers to find more valuable genes in the future research.

ObjectiveIntracranial vertebral artery terminated in the posterior inferior cerebellar artery (PICA-VA) is the most popular variant of the posterior inferior cerebellar artery, while its prevalence and clinical significance remained unclear. In the present study, we aimed to investigate the prevalence and clinical significance of PICA-VA.MethodsThis was a multicenter hospital-based cross-sectional study. Patients were enrolled for cerebral MRI and MRA within 1 week of stroke onset. Clinical characteristics were recorded. PICA-VA is termed as a vertebral artery that does not communicate with the basilar artery but terminates in an ipsilateral PICA. We observed the prevalence of PICA-VA and identified a relationship between PICA-VA and vertebrobasilar stroke.ResultsFrom 1 August 2015 to 31 May 2017, a total of 2,528 patients were enrolled in the present study. Among them, 95 patients (3.76%, 95/2,528) had the variation of PICA-VA, 51 of which (53.7%) were located on the right side. The prevalence of vertebrobasilar stroke was considerably higher in patients with PICA-VA than those without (40.2%, 37/92 vs. 17.1%, 417/2,436, p < 0.01). PICA-VA was an independent risk for vertebrobasilar stroke after being adjusted for a history of intracranial hemorrhage, diabetes, body mass index, and triglyceride.ConclusionThe present study showed that 3.76% of patients with acute stroke had PICA-VA, which independently increased the risk of acute vertebrobasilar stroke.

BackgroundEpilepsy is one of the leading neurological diseases. Our study is aimed to determine whether there is a focal region of high epilepsy prevalence in China.MethodsAll studies published between 1981 and 2020 investigating the prevalence of epilepsy in China were systematically reviewed. The geographical location, sample size, number of cases, urbanization rate, gross domestic product (GDP) per capita, percentage of

IntroductionHigh-resolution magnetic resonance imaging (HR-MRI) is used to characterize atherosclerotic plaque. The present study aimed to determine the high-risk features of the basilar artery (BA) atherosclerotic plaque.MethodsPatients with advanced BA stenosis were screened. The features including the ruptured fibrous cap (RFC), lipid core, intraplaque hemorrhage (IPH), plaque enhancement, and calcification were assessed by using high-resolution MRI. The relationship between the features and acute infarction was analyzed.ResultsFrom 1 June 2014 to 31 December 2018, a total of 143 patients with 76 new strokes were included. RFC was identified in 25% of symptomatic and 10.4% of asymptomatic patients. IPH was identified in 48.7% of symptomatic and 25.4% of asymptomatic patients. RFC (3.157, 95% CI 1.062 to 9.382, p = 0.039) and IPH (2.78, 95% CI 1.127 to 6.505, p = 0.026) were independent risk factors for acute infarction.ConclusionOur study showed that RFC and IPH of BA plaque were independent risk factors for acute infarction.

The ectonucleotidases CD38 and CD39 have a critical regulatory effect on tumors and viral infections via the adenosine axis. Natural killer (NK) cells produce cytokines, induce cytotoxic responses against viral infection, and acquire immunoregulatory properties. However, the roles of CD38 and CD39 expressed NK cells in HIV disease require elucidation. Our study showed that the proportions of CD38+CD39+ NK cells in HIV-infected individuals were positively associated with HIV viral loads and negatively associated with the CD4+ T cell count. Furthermore, CD38+CD39+ NK cells expressed additional inhibitory receptors, TIM-3 and LAG-3, and produced more TGF-β. Moreover, autologous NK cells suppressed the proliferation of CD8+ T and CD4+ T cells of HIV-infected individuals, and inhibiting CD38 and CD39 on NK cells restored CD8+ T and CD4+ T cell proliferation in vitro. In conclusion, these data support a critical role for CD38 and CD39 on NK cells in HIV infection and targeting CD38 and CD39 on NK cells may be a potential therapeutic strategy against HIV infection.

Abstract Background Antiretroviral therapy (ART) can reduce opportunistic infections and mortality rates among individuals infected with human immunodeficiency virus (HIV); however, some HIV-infected individuals exhibit poor immune recovery after ART. Hence, we explored the association between metabolome profiles and immune recovery in HIV-infected individuals following ART. Methods An untargeted metabolomics approach was used to analyze plasma samples from 18 HIV-negative individuals and 20 HIV-infected individuals, including 10 immunological non-responders (INR, CD4+ T cell rise 300 cells/μl) after 2 years of ART. These individuals were followed for the next 6 years and viral loads and CD4+ T cell count were measured regularly. Orthogonal projection on latent structures discriminant analysis (OPLS-DA), ANOVA, correlation, receiver operating characteristic (ROC), and survival analyses were used for selection of discriminant metabolites. Results Eighteen lipid metabolites were identified which could distinguish among control, INR, and IR groups. Among them, myristoylcarnitine (MC), palmitoylcarnitine (PC), stearoylcarnitine (SC), and oleoylcarnitine (OC) were significantly elevated in INR plasma samples compared with those from the IR and control groups and were negatively associated with CD4+ T cell count. Additionally, ROC analysis using a combination of MC, PC, SC, and OC had high sensitivity and specificity for differentiating INR from IR (AUC = 0.94). Finally, survival analysis for the combination of MC, PC, SC, and OC demonstrated that it could predict CD4+ T cell count in patients undergoing long-term ART. Conclusions High levels of lipid metabolites, MC, PC, SC, and OC are associated with poor immune recovery in patients receiving ART and these data provide potential new insights into immune recovery mechanisms.

Natural killer (NK) cells are crucial for immune responses to viral infections. CD160 is an important NK cell activating receptor, with unknown function in HIV infection. Here, we found that CD160 expression was reduced on NK cells from HIV-infected individuals and its expression was negatively correlated with HIV disease progression. Further, GLUT1 expression and glucose uptake were higher in CD160+ NK cells, and the results of RNA-seq and flow cytometry demonstrated that CD160 positively regulated glucose metabolism through the PI3K/AKT/mTOR/s6k signaling pathway, thereby enhancing NK cell function. Moreover, we determined that reduced CD160 expression on NK cells could be attributed to the higher plasma levels of TGF-β1 in HIV-infected individuals. Overall, these results highlight the vital role of CD160 in HIV disease progression and regulation of glucose metabolism, indicating a potential target for HIV immunotherapy.

Abstract Background T cell immunoglobulin and mucin domain-containing-3 (Tim-3) is a negative regulator expressed on T cells, and is also expressed on natural killer (NK) cells. The function of Tim-3 chiefly restricts IFNγ-production in T cells, however, the impact of Tim-3 on NK cell function has not been clearly elucidated. Results In this study, we demonstrated down-regulation of Tim-3 expression on NK cells while Tim-3 is upregulated on CD4+ T cells during HIV infection. Functional assays indicated that Tim-3 mediates suppression of CD107a degranulation in NK cells and CD4+ T cells, while it fails to inhibit the production of IFN-γ by NK cells. Analyses of downstream pathways using an antibody to block Tim-3 function demonstrated that Tim-3 can inhibit ERK and NFκB p65 signaling; however, it failed to suppress the NFAT pathway. Further, we found that the NFAT activity in NK cells was much higher than that in CD4+ T cells, indicating that NFAT pathway is important for promotion of IFN-γ production by NK cells. Conclusions Thus, our data show that the expression of Tim-3 on NK cells is insufficient to inhibit IFN-γ production. Collectively, our findings demonstrate a potential mechanism of Tim-3 regulation of NK cells and a target for HIV infection immunotherapy.

Abstract Background There is limited information about the types of recreational drugs used by men who have sex with men (MSM) in China or the consequent impact on sexual health and human immunodeficiency virus (HIV) acquisition. Methods We recruited MSM from seven cities in China between 2012 and 2013 using multiple approaches including advertisements on gay websites, collaborating with local MSM community-based organizations, peer referrals, and venues such as gay bars and bathrooms visited by MSM. We divided participants into four subgroups based on the number of recreational drugs (RDs) used in the previous 6 months. We defined use of multiple RDs as use of ≥2 types of RDs. Demographics and HIV-related high-risk behaviors were collected, and blood samples were tested for recent HIV infection by the HIV-1 subtypes B, E, and D immunoglobulin G capture enzyme immunoassay (BED-CEIA). We used multivariable logistic regression adjusted for sociodemographics to determine the adjusted odds ratios (aORs) and associated 95% confidence intervals (CIs) of the subgroups of RD use for recent or established HIV infection. Results A total of 4496 Chinese MSM participated; 28.4% used RDs, and 5% used multiple types of RDs. The prevalence of each RD use was as follows: poppers (25.9%), ecstasy (2.4%), ketamine (1.2%), amphetamine (0.6%), tramadol (0.4%), methamphetamine (3.8%), and codeine (1.9%). Users of multiple RDs commonly used poppers combined with one or more other types of RDs. Multiple RD users were likely to be aged 26–30 years (vs. 18–25 and > 30 years), live in non-local cities (vs. local cities), never married (vs. married), have a high monthly income (vs. no income and 1–599 USD), use versatile positions during anal intercourse (vs. top or bottom), and have inadequate HIV-related prevention knowledge (vs. adequate). As the number of RDs used in the previous 6 months increased, the prevalence of HIV-related high-risk behaviors increased (P

Abstract Background Rectal douching (RD) is widely practiced by men who have sex with men (MSM), and is associated with increased risk of HIV infection. However, the mechanism of how RD increases the risk of HIV infection is not well understood, and there is limited data on RD behavior in MSM practicing anal sex in China. We examine the purpose of RD, its timing in relation to anal sex, the types of RD products used, and risky sexual behaviors among MSM reporting anal sex. Methods Between August 2017 and December 2018, a cross-sectional study was conducted among adult MSM in Shenyang, China. Data were collected on demographics, sexual behaviors, and RD for the most recent sexual intercourse by means of interviewer-administered face-to-face questionnaires. Blood samples were collected to test for antibodies to HIV and syphilis. Multivariable logistic regression models were used to assess the risk factors associated with HIV infection. Results A total of 515 eligible MSM participated in this survey (median age: 31 years). During the most recent anal intercourse, 28.3% (146/515) had condomless receptive anal intercourse (CRAI), 21.4% (110/515) practiced serosorting, and more than half (61.6%, 317/515) reported RD before or after anal sex. Of those practicing RD, 96.8% (307/317) conducted RD before sex, while 62.5% (198/317) conducted RD after sex. The douching devices used were primarily shower hoses (85.3%, 262/307), and relatively few MSM used commercial RD products (8.1%, 25/307) before sex. The prevalence of HIV-1 and syphilis was 11.7% and 13.2%, respectively. HIV infection was positively associated with RD, practicing RD before sex, the interaction between RD and CRAI using a shower hose for RD and other risk factors, practicing RD after sex, CRAI, using nitrite inhalants, main sexual role with males as bottom and syphilis infection. Conclusions RD is popular among Chinese MSM. Improper noncommercial RD tools use (such as shower hose), the interaction effect between RD and CRAI associated with HIV infection. Public health workers and the MSM community should publicize scientific knowledge and prevention approaches relating to RD and HIV transmission to MSM. We recommend that further studies should be conducted to understand the detailed mechanism between RD and increased HIV prevalence.

Lipid-lowering is one of the most effective methods of prevention and treatment for cardiovascular diseases. However, most clinical lipid-lowering drugs have adverse effects and cannot achieve the desired efficacy in some complex hyperlipidemia patients, so it is of great significance to develop safe and effective novel lipid-lowering drugs. In the course of our project aimed at discovering the chemical novelty and bioactive natural products of marine-derived actinomycetes, we found that the organic crude extracts (OCEs) of Nocardiopsis sp. ZHD001 exhibited strong in vivo efficacies in reducing weight gain, lowering LDL-C, TC, and TG levels, and improving HDL-C levels in high-fat-diet-fed mice models. Chemical investigations of the active OCEs led to identifying two new sphydrofuran-derived compounds (1–2) and one known 2-methyl-4-(1-glycerol)-furan (3). Their structures were elucidated by the analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and ECD calculations. Among these compounds, compound 1 represents a novel rearranged sphydrofuran-derived derivative. Bioactivity evaluations of these pure compounds showed that all the compounds exhibited significant lipid-lowering activity with lower cytotoxicity in vitro compared to simvastatin. Our results demonstrate that sphydrofuran-derived derivatives might be promising candidates for lipid-lowering drugs.

Natural killer (NK) cells play an important immunologic role, targeting tumors and virus-infected cells; however, NK cells do not impede the progression of human immunodeficiency virus (HIV) infection. In HIV infection, NK cells exhibit impaired functions and negatively regulate other immune cell responses, although NK cells can kill HIV-infected cells and thereby suppress HIV replication. Considerable recent research has emerged regarding NK cells in the areas of immune checkpoints, negative regulation, antibody-dependent cell-mediated cytotoxicity and HIV reservoirs during HIV infection; however, no overall summary of these factors is available. This review focuses on several important aspects of NK cells in relation to HIV infection, including changes in NK cell count, subpopulations, and immune checkpoints, as well as abnormalities in NK cell functions and NK cell negative regulation. The protective function of NK cells in inhibiting HIV replication to reduce the viral reservoir and approaches for enhancing NK cell functions are also summarized.

Background. Pontine infarction is the major subtype of posterior circulation stroke, and diabetes is more common in pontine infarction patients than in anterior circulation stroke patients. Whether the prevalence of diabetes remains homogenous within the posterior circulation stroke population is unclear. The present study is aimed at investigating the prevalence of diabetes in pontine infarction and comparing it to other subtypes of posterior circulation stroke. Methods. We conducted a multicenter case-control study. Patients with posterior circulation stroke were screened. The subjects were divided into pontine infarction and nonpontine infarction groups. Results. From November 1, 2018, to February 28, 2021, a total of 6145 stroke patients were screened and 2627 patients had posterior circulation strokes. After excluding cardioembolic stroke, as well as its other determined and undetermined causes, 1549 patients with 754 pontine infarctions were included in the analysis. The prevalence of diabetes in the pontine infarction group was higher than that in the nonpontine infarction group (42.7% vs. 31.4%, P

Abstract Background Nitrite inhalant use is very common among men who have sex with men (MSM) in China. However, there is lack of national representative data on use among Chinese MSM, and the mechanism of how nitrite inhalant use impacts HIV infection in MSM is unclear. This meta-analysis aims to understand the characteristics of Chinese MSM nitrite inhalant users and to determine the associations between nitrite inhalant use and sexual behaviors, the prevalence of HIV, and the prevalence of syphilis. Methods We searched PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese Wanfang Data, and VIP Chinese Journal Database for relevant literature published from January 1985 to December 2017. Results Fifteen eligible studies, with a total of 18,981 Chinese MSM participants, were included. Compared with nitrite inhalant nonusers, users were more likely to be younger, have a higher level of education, and seek sexual partners using the Internet. Nitrite inhalant users were more likely to engage in high-risk sexual behaviors, including condomless anal intercourse (odds ratio [OR] = 1.33), group sex (OR = 2.26), and commercial intercourse (OR = 1.50). Nitrite inhalants users had a higher prevalence of HIV (OR = 1.83), higher prevalence of syphilis (OR = 1.38) and had higher lifetime HIV testing rates (OR = 1.33) compared with nonusers (each p

Abstract Background Pre-exposure prophylaxis (PrEP) is an effective biomedical strategy to prevent transmission of HIV infection, although medication adherence remains a challenge. We present the protocol for a multicentre randomised controlled trial to measure the effectiveness of a real-time monitoring and just-in-time intervention on medication adherence among PrEP users in China. Methods Study participants will include 1000 men who have sex with men (MSM) from four cites in China (Shenyang, Beijing, Chongqing and Shenzhen) attending a tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) PrEP project as part of a real-world, prospective multicentre cohort study (CROPrEP). Participants will be randomised into the intervention and control arms in a 1:1 ratio. Participants in the intervention arm will be provided with remote real-time monitoring equipment that triggers twice just-in-time SMS (Short Messaging Service) medication reminders to PrEP users every half an hour when a scheduled dosage is missed, and followed with just-in-time SMS medication reminders to clinicians half an hour when there is no supplement after the second just-in-time SMS reminder to PrEP users. Clinicians will initiate individualised telephone intervention as soon as possible upon receipt of the just-in-time SMS missed dose alert. Those in the control arm will only receive generic weekly SMS reminders. The study will last 6 months. Participants will be seen at follow-up visits at three and 6 months. Trial outcomes to be measured include self-reported adherence assessed via questionnaire and pill counts, as well as drug concentration test results. Discussion Medication adherence is critical to achieve optimal benefits from PrEP. This study will be the first individualised behaviour intervention using real-time technology to increase adherence among MSM PrEP users globally. If found effective, a real-time monitoring and just-in-time intervention system may be utilized for improving adherence and thus effectiveness of global PrEP application. Trial registration This study registered at ClinicalTrials.gov ( ChiCTR1900025604 ) on September 2, 2019.

Abstract Background Chemokines are small chemotactic cytokines involved in inflammation, cell migration, and immune regulation in both physiological and pathological contexts. Here, we investigated the profile of chemokines during primary HIV infection (PHI). Methods Fifty-four participants with blood samples before and during HIV infection and clinical information available were selected from an HIV-negative man who have sex with men (MSM) prospective cohort. Thirty chemokines and 10 cytokines were measured pre- and post-HIV infection in the same individuals using a Bio-Plex Pro™ Human Chemokine Panel. Results Levels of 18 chemokines/cytokines changed significantly during PHI relative to pre-HIV infection levels; 14 were up-regulated and 4 down-regulated. Among them, CXCL9, CXCL10, and CXCL11 were the most prominently raised. Levels of CXCL9 and CXCL10 were much higher in the high-set point group (log viral load (lgVL) ≥ 4.5) than those in the low-set point group (lgVL

BackgroundHIV self-testing (HIVST) kits are common in key sexually active populations. Direct secondary distribution of HIVST kits (DSDHK) is effective in improving the uptake of HIVST. However, there are concerns about the various limitations of DSDHK, including limited geographic reach, payment problems, and need for face-to-face interactions. ObjectiveIn this study, we aim to evaluate the feasibility and characteristics of indirect secondary distribution of HIVST kits (ISDHK) via WeChat (distributing HIVST application links and follow-up HIVST kits to partners) among men who have sex with men (MSM). MethodsFrom October 2017 to September 2019, an HIVST recruitment advertisement was disseminated on the WeChat social media platform to invite MSM to apply for the HIVST kits (referred to as index participants [IPs]). All MSM participants were encouraged to distribute the HIVST application link to their friends and sexual partners (referred to as alters) through their social networks. All the alters were further encouraged to continue distributing the HIVST application link. All participants paid a deposit (US $7), which was refundable upon completion of the questionnaire, and uploaded the test results via a web-based survey system. ResultsA total of 2263 MSM met the criteria and successfully applied for HIVST. Of these, 1816 participants returned their HIVST results, including 1422 (88.3%) IPs and 394 (21.7%) alters. More alters had condomless anal intercourse, a higher proportion of them had never previously tested for HIV, and they showed a greater willingness to distribute HIVST kits to their sexual partners (P=.002) than the IPs. After controlling for age, education, and income, the alters had a greater proportion of MSM who had never tested for HIV before (adjusted odds ratio [aOR] 1.29, 95% CI 1.00-1.68), were more willing to distribute the HIVST application link (aOR 1.71, 95% CI 1.21-2.40), had a lower number of sexual partners (aOR 0.71, 95% CI 0.57-0.90), and were less likely to search for sexual partners on the web (aOR 0.78, 95% CI 0.60-1.02) than IPs. In comparison, the rates of reactive HIVST results, conducting HIV confirmatory tests, HIV seropositivity, and initiation of HIV antiretroviral therapy were similar for IPs and alters. ConclusionsThe ISDHK model of distributing HIVST application links among the MSM population via social media is feasible. The ISDHK model should be used to supplement the DSDHK model to enable a greater proportion of the MSM population to know their HIV infection status.

Plaque rupture of the basilar artery is one of the leading causes of posterior circulation stroke. The present study aimed to investigate the role of fluid dynamics in the ruptured fibrous cap of basilar artery plaques. Patients with basilar artery plaques (50–99% stenosis) were screened. Integrity of the fibrous cap was assessed by high-resolution MRI. Computational fluid dynamics models were built based on MR angiography to obtain the wall shear stress and velocity. A total of 176 patients were included. High-resolution MRI identified 35 ruptured fibrous caps of basilar artery plaques. Ruptured fibrous cap was significantly associated with acute infarction (27/35 vs. 96/141, p < 0.05) in the territory of the basilar artery. Proximal wall shear stress of stenosis was positively related with the ruptured fibrous cap (OR 1.564; 95% CI, 1.101–2.222; p = 0.013). The threshold of wall shear stress for the ruptured fibrous cap of basilar artery plaques was 4.84 Pa (Area under ROC 0.732, p = 0.008, 95%CI 0.565–0.899). The present study demonstrated that increased proximal wall shear stress of stenosis was associated with ruptured fibrous caps of basilar artery plaques.

Cistanche is a medicinal and food homologous substance with a long history of consumption and medicinal use in China. In order to further understand the volatile organic compound differences between different cistanches, this study selected oil cistanche, blood cistanche and cistanche tubulosa in Xinjiang for HS-GC-IMS volatile organic compounds, and established the characteristic fingerprints of different cistanches for organic content and characteristic organic compound analysis. PCA and cluster analysis were used to study the similarity between different cistanches. After qualitative analysis, a total of 32 volatile organic compounds were identified, covering aldehydes (17), ketones (5), furans (1), alcohols (5), lactones (1) and esters (3), and the volatile organic compounds between samples a, b and c could be significantly distinguished, affecting the flavor of cistanche itself. It provides a basic theoretical basis for the study of cistanche flavor.

BackgroundRoutine HIV testing accompanied with pre-exposure prophylaxis (PrEP) requires innovative support in a real-world setting. ObjectiveThis study aimed to determine the usage of HIV self-testing (HIVST) kits and their secondary distribution to partners among men who have sex with men (MSM) in China, who use PrEP, in an observational study between 2018 and 2019. MethodsIn 4 major cities in China, we prospectively followed-up MSM from the China Real-world oral PrEP demonstration study, which provides daily or on-demand PrEP for 12 months, to assess the usage and secondary distribution of HIVST on quarterly follow-ups. Half of the PrEP users were randomized to receive 2 HIVSTs per month in addition to quarterly facility-based HIV testing. We evaluated the feasibility of providing HIVST to PrEP users. ResultsWe recruited 939 MSM and randomized 471 to receive HIVST, among whom 235 (49.9%) were daily and 236 (50.1%) were on-demand PrEP users. At baseline, the median age was 29 years, 390 (82.0%) men had at least college-level education, and 119 (25.3%) had never undergone facility-based HIV testing before. Three months after PrEP initiation, 341 (74.5%) men had used the HIVST provided to them and found it very easy to use. Among them, 180 of 341 (52.8%) men had distributed the HIVST kits it to other MSM, and 132 (51.6%) among the 256 men who returned HIVST results reported that used it with their sexual partners at the onset of intercourse. Participants on daily PrEP were more likely to use HIVST (adjusted hazard ratio=1.3, 95% CI 1.0-1.6) and distribute HIVST kits (adjusted hazard ratio=1.3, 95% CI 1.1-1.7) than those using on-demand PrEP. ConclusionsMSM who used PrEP had a high rate of usage and secondary distribution of HIVST kits, especially among those on daily PrEP, which suggested high feasibility and necessity for HIVST after PrEP initiation. Assuming that fourth-generation HIVST kits are available, HIVST may be able to replace facility-based HIV testing to a certain extent. Trial RegistrationChinese Clinical Trial Registry ChiCTR1800020374; https://www.chictr.org.cn/showprojen.aspx?proj=32481 International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2019-036231

A major barrier to HIV eradication is the persistence of viral reservoirs. Resting CD4+ T cells are thought to be one of the major viral reservoirs, However, the underlying mechanism regulating HIV infection and the establishment of viral reservoir in T cells remain poorly understood. We have investigated the role of IP-10 in the establishment of HIV reservoirs in CD4+ T cells, and found that in HIV-infected individuals, plasma IP-10 was elevated, and positively correlated with HIV viral load and viral reservoir size. In addition, we found that binding of IP-10 to CXCR3 enhanced HIV latent infection of resting CD4+ T cells in vitro. Mechanistically, IP-10 stimulation promoted cofilin activity and actin dynamics, facilitating HIV entry and DNA integration. Moreover, treatment of resting CD4+ T cells with a LIM kinase inhibitor R10015 blocked cofilin phosphorylation and abrogated IP-10-mediated enhancement of HIV latent infection. These results suggest that IP-10 is a critical factor involved in HIV latent infection, and that therapeutic targeting of IP-10 may be a potential strategy for inhibiting HIV latent infection.

Summary: Although peripheral B cell dysfunction in early HIV infection is established, how B cell subsets are altered by HIV infection is poorly understood. While investigating B cell subsets among individuals recently infected with HIV, we observe an accumulation of CD27−CD38+ B cells and find that these cells can directly facilitate HIV infection of primary CD4+ T cells in vitro. Comprehensive analyses of the phenotype, function, and transcriptome of the CD27−CD38+ B cell subset is conducted compared with memory and naive B cells. We find that the CD27−CD38+ B cells exhibit a transitional B cell phenotype and an extremely high turnover rate. Importantly, individuals with higher proportions of CD27−CD38+ B cells during early HIV infection tend to become rapid progressors in the chronic infection stage. In this study, we identify a peripheral transitional B cell subset that accumulates during early HIV infection and may contribute to disease progression.

Background: Post-stroke depression (PSD) is a common complication of stroke, which seriously affects the functional outcome of patients. Systemic low-grade inflammation associated with PSD has been shown to occur at several months to years, however, whether these inflammatory markers predicted PSD at an acute stage of stroke is controversial. Method: A total of 625 patients with acute ischemic stroke (219 female, 35.40%) were included in this study. PSD was diagnosed using the 17-item Hamilton depression scale (HAMD) at 7 days following discharge (7–14 days after stroke onset). Multivariable logistic regression analysis was applied to build a prediction model for PSD at discharge. Discrimination and calibration of the model were assessed by C-index, calibration plot. Internal validation was conducted using bootstrapping validation. Results: At discharge of hospitalization, 95 patients (15.20%) were diagnosed with PSD. Multivariable logistic regression suggested that female gender (OR = 2.043, 95% CI = 1.287–3.245, p = 0.002), baseline NIHSS (OR = 1.108, 95% CI = 1.055–1.165, p < 0.001) and fibrinogen (OR = 1.388, 95% CI = 1.129–1.706, p = 0.002) were independent predictors for PSD at discharge. The cut-off of the fibrinogen plasma level was 3.08 g/L. These predictors were included in the nomogram. The model displayed good discrimination, with a C-index of 0.730 (95% CI = 0.683–0.777) and good calibration. Conclusion: Female gender, baseline stroke severity and a higher level of fibrinogen were independently associated with PSD at discharge. A nomogram based on these three predictors can be used to provide an individual, visual prediction of the risk probability of PSD.

Abstract Background The topographic location of acute pontine infarction is associated with clinical syndromes and prognosis. Previous studies focused on isolated pontine infarction, but the topographic location of unisolated pontine infarction has remained unclear. Methods This was a prospective, multicenter, longitudinal registry study. Patients with acute pontine infarction confirmed by magnetic resonance imaging (MRI) were enrolled. Based on the territory of the pontine artery, the topographic location was divided into anteromedial, anterolateral, tegmental, bilateral and unilateral multiple infarctions. Results From May 1, 2003, to Oct 31, 2017, 1003 patients were enrolled, and 330 had unisolated pontine infarction. For isolated pontine infarction, 44.9, 19.8, 16.0, 13.1 and 6.2% of patients had anteromedial, anterolateral, tegmental, bilateral and unilateral multiple pontine infarctions, respectively. For unisolated pontine infarction, 30.3, 19.7, 24.5, 15.2 and 10.3% of patients had anteromedial, anterolateral, tegmental, bilateral and unilateral multiple pontine infarctions, respectively. Conclusion In this large series study, our data revealed fewer anteromedial infarctions and more tegmental and unilateral multiple infarctions in patients with unisolated pontine infarction than in patients with isolated pontine infarction.

Abstract Background Functions of astrocytes in the rehabilitation after ischemic stroke, especially their impacts on inflammatory processes, remain controversial. This study uncovered two phenotypes of astrocytes, of which one was helpful, and the other harmful to anoxic neurons after brain ischemia. Methods We tested the levels of inflammatory factors including TNF-a, IL-6, IL-10, iNOS, IL-1beta, and CXCL10 in primary astrocytes at 0 h, 6 h, 12 h, 24 h, and 48 h after OGD, grouped the hypoxia astrocytes into iNOS-positive (iNOS(+)) and iNOS-negative (iNOS(−)) by magnetic bead sorting, and then co-cultured the two groups of cells with OGD-treated neurons for 24 h. We further verified the polarization of astrocytes in vivo by detecting the co-localization of iNOS, GFAP, and Iba-1 on MCAO brain sections. Lentivirus overexpressing LCN2 and LCN2 knockout mice (#024630. JAX, USA) were used to explore the role of LCN2 in the functional polarization of astrocytes. 7.0-T MRI scanning and the modified Neurological Severity Score (mNSS) were used to evaluate the neurological outcomes of the mice. Results After oxygen-glucose deprivation (OGD), iNOS mRNA expression increased to the peak at 6 h in primary astrocytes, but keep baseline expression in LCN2-knockout astrocytes. In mice with transient middle cerebral artery occlusion (tMCAO), LCN2 was proved necessary for astrocyte classical activation. In LCN2 knockout mice with MCAO, no classically activated astrocytes were detected, and smaller infarct volumes and better neurological functions were observed. Conclusions The results indicated a novel pattern of astrocyte activation after ischemic stroke and lipocalin-2 (LCN2) plays a key role in polarizing and activating astrocytes.

Abstract Background Pre-exposure prophylaxis (PrEP) is a promising and effective tool to prevent human immunodeficiency virus (HIV) transmission; however, context-specific data to guide optimal implementation are currently lacking in China. This study aims to systematically collect comprehensive, empirical data to determine effective ways to implement PrEP among at-risk men who have sex with men (MSM) in China. Methods The CROPrEP project, a real-world study of PrEP use, will recruit 1000 high-risk HIV-negative MSM participants from four cities in China, who will be able to choose between daily or event-driven dosing regimens, according to their preference. Participants will be followed up at months 1, 3, 6, 9, and 12 for PrEP provision, clinical evaluation, laboratory testing (e.g., emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) concentrations, and HIV/sexually transmitted infections), alongside detailed, self-administered online questionnaires regarding sexual behaviors, adherence, and attitudes. Online weekly notes will be used to record pill use and sexual practice. Various measurements will be triangulated to assess adherence, including: self-reported adherence, pill count, and drug concentration. A propensity score matching model will be fitted to examine the effectiveness of PrEP use in HIV seroconversion compared with non-PrEP users selected from a local expanding cohort study of HIV-1-negative MSM at participating research centers. Analyses using a generalized estimating equation model will focus on elucidation of the cascade of PrEP implementation, effectiveness, safety, and possible effects of PrEP use on sexual behaviors. This study will provide a comprehensive assessment of real-world PrEP use among Chinese MSM, to develop guidelines and strategies for PrEP implementation in China. Discussion The CROPrEP project is the first study of the TDF/FTC combination as PrEP in China, which will provide primary data on PrEP implementation, including: the cascade of PrEP use, “real-world” effectiveness, adherence, and safety. The findings from this study have potential to be vital for promoting the integration of PrEP within the portfolio of HIV prevention interventions and developing guidance on PrEP implementation in China. Trial registration ChiCTR-IIN-17013762 (Chinese Clinical Trial Registry). Date of registration: 8 December 2017.

Abstract Background Body mass index (BMI) may contribute somewhat to drug metabolism, and thus affecting the efficacy of highly active antiretroviral therapy (HAART). This study aimed to determine the frequencies of underweight, normal and overweight/obesity at pre-HAART in a large cohort of HIV-infected Chinese patients, and investigate the prospective effects of BMI on immune reconstitution after HAART initiation. Methods A longitudinal cohort study was performed to analyze the effects of BMI on immune reconstitution in HIV-infected patients treated with HAART. Multiple linear regression was used to evaluate the relationship between baseline BMI and increased CD4+ T lymphocyte levels at 12 and 30 months after initiating HAART. In addition, Cox proportional hazard model was used to assess the relationship between BMI and time to achieve immunologic reconstitution (CD4+ T lymphocytes>500cells/μL) during the follow-up period. Results Among the 1612 enrolled patients, 283 (17.6%) were overweight/obese (BMI ≥ 25 kg/m2), 173 (10.7%) were underweight (BMI

Although pontine infarction is the most common subtype of posterior circulation stroke, there has been little research focusing on recurrent pontine infarction. Our study aimed to investigate the factors associated with site and mechanism of recurrent pontine infarction. Patients with acute isolated pontine infarction were enrolled and followed up for one year. Lesion topography was determined by diffusion-weighted imaging. Mechanisms were determined based on lesion topography and other vascular, cardiologic and laboratory results. A total of 562 patients with pontine infarction were included, with 67 patients experiencing recurrence during the follow-up period. Forty-one recurrences occurred at the same site as index pontine infarction (41/67, 61.2%). Results indicated that the mechanism of index pontine infarction was significantly associated with the recurrent sites (p = 0.041, OR 2.938, 95% CI 1.044–8.268), and also with the mechanisms of recurrence (p = 0.004, OR 6.056, 95% CI 1.774–20.679). Branch atheromatous disease-induced index pontine infarction was likely to recur at the same site and with the same mechanism. Moreover, if recurrence occurred at the same site, the mechanism was probably the same as that of the index stroke (p = 0.000). Our study may help physicians treat patients with pontine infarction by predicting the site and mechanism of recurrence.

General greening in vegetation, especially in southwest China, has been observed globally in recent decade. However, temporal-spatial variation patterns and potential causes of vegetation greening are not well understood in southwest China. Here, we used data of the normalized difference vegetation index (NDVI) and climate, land use and land cover, geology, ecological afforestation and karst rocky desertification to analyze the temporal-spatial variation patterns in vegetation coverage and its response to climate change and human-induced factors in southwest China between 2000 and 2016. A general greening trend in vegetation, with significant differences in temporal-spatial variation patterns, was observed in southwest China from 2000 to 2016, and the area of significant vegetation greening from 2006 to 2016 increased by 4.68% relative to the level from 2000 to 2005. The increased proportion of significant vegetation greening was higher in the karst regions (6.95%), especially in the limestone region (8.00%), than in the nonkarst region (3.82%). Of all the vegetation greening trends, 65% was associated with human-induced factors, and 35% was resulted from climate change from 2000 to 2005. After the implementation of karst ecological restoration engineering, the contribution of human-induced factors to vegetation greening increased to 77% from 2006 to 2016, although southwest China experienced a serve drought during that time. These results highlight that karst ecological engineering projects can reduce the risks of desertification and karst ecosystem sensitivity to climate perturbations.

Introduction Pre-exposure prophylaxis (PrEP) reduces the risk of HIV infection among men who have sex with men by up to 99%. However, in real-world settings, PrEP users may exhibit risk compensation after uptake of PrEP, including more condomless anal intercourse (CAI) and increased sexually transmitted infection (STI) acquisition. HIV self-testing (HIVST) decreases CAI among men who have sex with men (MSM) by providing awareness of the HIV status of oneself and one’s sexual partners. Here, we describe the rationale and design of a randomised waitlist-controlled trial to examine the impact of HIVST on risk compensation among PrEP users.Methods and analysis The study is a two-arm randomised waitlist-controlled trial with 1000 HIV-negative MSM in four major cities in China who will be taking oral PrEP (involving tenofovir disoproxil fumarate/emtricitabine) either daily (n=500) or in an event-driven regimen (n=500). The participants will be randomised (1:1) to either the immediate HIVST intervention arm (HIVST plus standard facility-based counselling and testing from 0 to 12 months) or the waitlist arm (standard facility-based counselling and testing from 0 to 6 months, then crossover to receive the HIVST intervention in months 7–12). Participants will provide blood samples to assess the incidence of syphilis and herpes simplex virus type 2 (HSV-2) during a follow-up. The primary outcomes will be the occurrence of CAI, number of sexual partners and incidence of syphilis and HSV-2 during a follow-up. The secondary outcomes will be the HIV and STI testing frequency and STI treatment adherence during a follow-up. The planned start and end dates for the study is 26 December 2018 and 31 December 2020.Ethics and dissemination The Medical Science Research Ethics Committee of The First Affiliated Hospital of China Medical University has approved the study (IRB(2018)273).Trial registration number ChiCTR1800020374

A horseshoe kidney is a congenital kidney malformation commonly associated with complications such as hydronephrosis, renal calculi, and infections of the renal pelvis. Renal cell carcinoma is extremely rare in a horseshoe kidney; once it occurs, however, it is intractable because of vascular abnormalities. This is especially true in laparoscopic nephron-sparing surgery, even for tumors of

Abstract Background Natural killer (NK) cells play cytotoxic roles by targeting tumor cells or virus infected cells, they also play regulatory roles by secreting cytokines and chemokines. Transforming growth factor (TGF)-β and interleukin (IL)-10 are important immunosuppressive cytokines potentially related to the immune dysregulation that occurs in the infection of human immunodeficiency virus (HIV). NK cells are an important source of TGF-β and a main early producer of IL-10 in response to viral infection. Here, we evaluated the percentages of IL-10+ and TGF-β+ NK cells in HIV-infected patients relative to healthy controls (HCs). Methods Study participants (n = 63) included 31 antiretroviral treatment (ART)-naïve HIV-infected patients, 17 ART-treated HIV-infected patients, and 15 HIV-negative HCs. Expression of IL-10 or TGF-β in NK cells was examined by flow cytometry, and the influences of recombinant IL-10 (rIL-10) or recombinant TGF-β (rTGF-β) on NK cell function were investigated in vitro. Results Compared with HCs, ART-naïve HIV-infected patients had increased percentages of IL-10+ (2.0% vs. 0.4%, p = 0.015) and TGF-β+ (4.5% vs. 2.1%, p = 0.022) NK cells, and ART-treated patients also had a higher percentage of IL-10+ NK cells (2.5% vs. 0.4%, p = 0.002). The percentages of IL-10+ and TGF-β+ NK cells were positively correlated (r = 0.388; p = 0.010). The results of in vitro experiments demonstrated that rIL-10 and rTGF-β inhibited NK cell CD107a expression (p = 0.037 and p = 0.024, respectively), IFN-γ secretion (p = 0.006, p = 0.016, respectively), and granzyme B release after stimulation (p = 0.014, p = 0.040, respectively). Conclusions Our data suggest that the percentages of IL-10+ or TGF-β+ NK cells are increased in HIV-infected patients, and that rIL-10 and/or rTGF-β can inhibit NK cell functions in vitro, providing a potential therapeutic target for strategies aimed at combating HIV infection.

Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response largely mediated by natural killer (NK) cells that can lyse target cells and combat tumors and viral infections. However, the role of ADCC in response to primary HIV infection is poorly understood. In the present study, we explored the ADCC response and evaluated its characteristics in 85 HIV-infected individuals, including 42 with primary infections. Our results showed that ADCC occurs during acute infection, and the earliest ADCC response to a single peptide was detected at 52 days. Primary HIV-infected individuals exhibiting ADCC responses had lower viral set points than those with no ADCC response, and functional analyses demonstrated that the ADCC response could significantly inhibit viral infection during primary HIV infection. HIV epitopes that provoked the ADCC response were determined and three relatively conserved epitopes (HNVWATYACVPTDPNPQE, TSVIKQACPKISFDPIPI, and VVSTQLLLNGSLAEEEII) from the surface of the three-dimensional structure of the HIV Env protein were identified. Overall, our data indicate that ADCC responses may be significant for the control of HIV from an early stage during infection. These findings merit further investigation and will facilitate improvements in vaccines or therapeutic interventions against HIV infection.

Natural killer (NK) cells are important for maintenance of innate immune system stability and serve as a first line of defense against tumors and virus infections; they can act either directly or indirectly and are regulated via co-operation between inhibitory and stimulatory surface receptors. The recently reported inhibitory receptor, TIGIT, can be expressed on the NK cell surface; however, the expression level and function of TIGIT on NK cells during HIV infection is unknown. In this study, for the first time, we investigated the expression and function of TIGIT in NK cells from HIV-infected individuals. Our data demonstrate that the level of TIGIT is higher on NK cells from patients infected with human immunodeficiency virus (HIV) compared with HIV-negative healthy controls. TIGIT expression is inversely correlated with CD4+ T cell counts and positively correlated with plasma viral loads. Additionally, levels of the TIGIT ligand, CD155, were higher on CD4+ T cells from HIV-infected individuals compared with those from healthy controls; however, there was no difference in the level of the activating receptor, CD226, which recognizes the same ligands as TIGIT. Furthermore, TIGIT was found to specifically up-regulated on CD226+ NK cells in HIV-infected individuals, and either rIL-10, or rIL-12 + rIL-15, could induce TIGIT expression on these cells. In addition, high TIGIT expression inhibited the production of interferon-gamma (IFN-γ) by NK cells, while TIGIT inhibition restored IFN-γ production. Overall, these results highlight the important role of TIGIT in NK cell function and suggest a potential new avenue for the development of therapeutic strategies toward a functional cure for HIV.